Even moderate leisure-time physical activity may protect against 13 cancers, according to a massive observational study that appeared May 16 in JAMA Internal Medicine (doi:10.1001/jamainternmed.2016.1548).

But which type of exercise brings the most benefit is not yet clear, researchers say, nor is exercise alone likely to account for its association with a lower cancer risk in colon, breast, and endometrial cancers, among others.

“Physical activity is not a stand-alone, magic bullet,” said William McCarthy, Ph.D., adjunct professor in the department of health services in the Fielding School of Public Health at the University of California, Los Angeles. “The biggest bang [in risk reduction] comes when exercise is coupled with a Mediterranean-style diet and not smoking.”

Still, McCarthy said, the recent joint study by researchers at the National Cancer Institute and the American Cancer Society highlights exercise’s importance to cancer risk and overall health, despite what he described as years of skepticism in the scientific community. “It’s a shot in the arm for those of us doing exercise studies for years,” he said.

Researchers at both organizations analyzed pooled data for the self-reported leisure-time physical activities of 1.44 million people in 12 U.S. and European studies conducted between 1982 and 2004. Analyzing data from those combined studies gave investigators greater statistical power than a single study.

“Most of the data in our study had never before been published, or in many cases, results had been published early on, but with no follow-up,” said Steven C. Moore, Ph.D., M.P.H., lead author and an investigator at NCI. “By pooling the data ourselves, we were able to pick and choose what to study, allowing us to produce stronger findings and minimizing heterogeneity.”

Median follow-up time was 11 years. During that period, roughly 186,000 new cases of cancer occurred—the highest numbers seen in those cancers with the highest incidence in the general population as well: prostate, breast cancer, lung cancer, and colon cancer.

Each of the 12 studies had a common theme, with the general understanding that exercises were done only for fitness, not as part of daily activities, Moore said. Also, in each study, investigators compared the metabolic activity expended, grouping people by percentile from most active to least active. Most people in the studies, Moore said, engaged in moderate activity, primarily walking, expending roughly three times the number of calories used while sitting.

The median among participants was 150 minutes per week of moderate-intensity activity. That level dovetails with the minimum level of exercise that the U.S. government recommends—that, or 75 minutes each week of vigorous, heart-pumping activities, such as running or swimming.

Moore described the nation’s physical activity guidelines as “spot-on.” But for other outcomes, such as weight loss, or potentially stronger cancer prevention, the levels of physical activity should be higher, he said.

Future studies will look at the type, intensity, and volume of exercise that bring the best results, Moore said, adding “all three still need better characterization.”

Rising Benefit

The authors looked at how exercise affected 26 cancers. In general, people who exercised more saw an association with a 7% lower risk of developing any type of cancer, compared with more sedentary individuals, despite the known limitations of self-reporting. But the most compelling finding was that the most active exercisers—those in the top 10% of the statistical analysis—were at least 20% less likely than the least active to develop certain cancers, including esophageal, stomach, kidney, and liver cancers. And the data confirmed a lowered risk for colon, breast, and endometrial cancers, as hundreds of studies have suggested.

Overall, the investigators observed the strongest association between exercise and lower cancer risk in esophageal adenomas (a 42% lower risk) and the weakest in two malignancies, melanoma and prostate cancer.

“Exercise is very consistently associated with reduced inflammation, not only for all cancers, but all conditions, including heart disease, diabetes, and even Alzheimer’s disease.”

Prostate cancer showed evidence of a modestly higher association with cancer risk among men who exercised more, said Alpa Patel, Ph.D., a coauthor and investigator at the American Cancer Society in Atlanta. “But we don’t believe that to be a biologically true finding,” she said. “Physically active men are far more likely to be screened and, if you’re screened, you see more cancers.”

Similarly, researchers attributed the small spike in melanoma to certain habits of more-active individuals: not only an increased likelihood of screening but also, during exercise, more exposure to the sun’s UV rays.

One surprising finding concerned body mass index, which made little difference in results. But the finding did not mean that no independent protective effect was present even in obese or overweight individuals who exercised actively, only slightly less than anticipated, Patel said.

For example, the top exercisers had a 16% lower risk than the least active of developing colon cancer, without adjusting for body mass index, she said. But after researchers accounted for this variable, the risk still remained 13% lower in the physically active group.

“One of the most exciting things about our study is it boosts the benefits of exercise much more broadly” to the general population, Patel said.

Metabolic Pathways

Exactly how exercise exerts its beneficial effects in cancer risk remains an area of active research.

Moore said he and his colleagues generally believe that changes in sex hormones, insulin resistance, and inflammation are the mechanisms through which exercise protects against cancer.

A more precise understanding of these mechanisms “would not only strengthen the biological plausibility of the physical activity–cancer association, but could aid in identifying molecular targets for intervention,” wrote Marilie Gammon, Ph.D., an epidemiologist from the Gillings School of Global Public Health in Chapel Hill, N.C., in an editorial accompanying the study. But although Gammon praised the researchers for their work, she noted that physical activity is “just one of a cluster of healthy behaviors” that may contribute to their findings.

McCarthy agreed, citing a good diet as one healthy behavior, needing further emphasis because of its close interaction with the inflammatory response. “Exercise is very consistently associated with reduced inflammation, not only for all cancers, but all conditions, including heart disease, diabetes, and even Alzheimer’s disease,” McCarthy said. And although exercise lowers inflammation in the gut, its presence can undercut a good diet, he said, illustrating how closely the two work together to ensure good health.

“In this study, the organs most affected are the digestive organs, and they disproportionately interact with nutrition,” so that should be the focus in the future, along with smoking status, McCarthy said. “Now, thanks to the microbiome, we can get a more nuanced view—opening up a whole string of new opportunities.”

Articles from JNCI Journal of the National Cancer Institute are provided here courtesy of Oxford University Press